Genome-wide association analysis of 350,000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.

Abstract

The disease risk for asthma, hay fever and eczema include both environmental and genetic risk factors and the comorbidity between the diseases are large. Heritability estimates suggest that the risk of asthma, hay fever and eczema is largely due to genetic factors. In this GWAS, we include 346,545 Caucasian participants from the UK Biobank to increase power to identify novel loci for asthma, hay fever and eczema. We also investigate if associated lead SNPs have a significantly larger effect for one disease phenotype compared to the other phenotypes, to highlight possible disease specific effects.\n\nThis study identifies 141 loci, of which 41 are novel to this study, to be associated (P[≤]3x10-8) with asthma, hay fever or eczema, analysed separately or combined as a single phenotype. At four of the novel loci, TNFRSF8, MYRF, TSPAN8, and BHMG1, the lead SNPs were in LD (> 0.8) with potentially casual missense variants. For seven of the novel GWAS loci, the lead SNP was in LD (> 0.8) with genetic variants associated with gene expression (eQTL) where, for example, increased levels of TMEM258 as well as decreased levels of HHEX and ADAM19 was associated with decreased odds for asthma.\n\nOur study shows that a large amount of the genetic contribution to asthma, hay fever and eczema is shared between the diseases. Nonetheless, a number of SNPs have a significantly larger effect on one of the phenotypes suggesting that part of the genetic contribution is more phenotype specific.